Enhancing the efficacy of anti-malarial drugs with immune boosters: A mathematical model

Abstract

<abstract> <p>This paper presents a mathematical model of severe malarial anemia (SMA), which is a complication of malaria and is a major contributor to malaria-related deaths. SMA is characterized by a decrease in hemoglobin levels in the blood due to the suppression of red blood cell (RBC) recruitment by the protein macrophage migration inhibitory factor (MIF). Plasmodium falciparum, which is a malaria-causing parasite, secretes a specific form of MIF called plasmodium falciparum macrophage migration inhibitory factor (PFMIF), which affects immune cells. Artesunate, which is the primary treatment for SMA, reduces the parasite level but does not increase hemoglobin levels and can sometimes lead to hemolytic anemia, which requires a blood transfusion. To address this issue, the experimental drug Epoxyazadiradione (Epoxy) was explored as a potential treatment for SMA. Epoxy inhibits both MIF and PFMIF interactions with immune cells and has the potential to increase hemoglobin levels in SMA patients. Our model simulations support previous findings that the appropriate combination of Artesunate with Epoxy can reduce parasite load while preventing anemia by maintaining hemoglobin levels at an adequate level. Additionally, we explored the impact of immune boosters on the anti-malarial drugs Artesunate and Epoxy and discovered that an insufficient amount of drugs is ineffective, while an excessive amount may not be beneficial.</p> </abstract>